Clinical features and diagnosis of 42 travellers with cutaneous leishmaniasis.

BACKGROUND: Leishmania species that occur within different geographical areas may cause different clinical manifestations, virulence and drug sensitivity. Patients/Methods. All patients with a clinical diagnosis of cutaneous leishmaniasis seen at the Hospital for Tropical Diseases from 1997 to 2000 were identified and clinical details recorded onto a database, with emphasis on clinical presentation, risk factors, travel history and laboratory diagnosis. RESULTS: Forty-two patients were identified, 23 of whom had travelled to New World and 19 to Old World countries. Clinical presentation typically consisted of a single nodule with ulceration. In 50% infection was caused by L. (Viannia) braziliensis. PCR was performed in specimens from 34 patients and species identification was possible in 32 cases (sensitivity 94%), the two PCR negative patients had amastigotes demonstrated by histology and culture. Patients were treated with established therapies. Seventy one percent were cured by treatment, 12% had a spontaneous cure, 7% were lost to follow-up and the remaining 10% required a second-line therapy. No relapses were reported during a mean follow-up period of 27 months. CONCLUSIONS: Our study highlights the need for comprehensive investigations and the advantages of PCR in the diagnosis of patients with suspected leishmaniasis in non-endemic regions of the world.

Miltefosine: issues to be addressed in the future.

Future issues that need to be addressed for miltefosine are efficacy against non-Indian visceral leishmaniasis, efficacy in HIV-coinfected patients, efficacy against the many forms of cutaneous and mucosal disease, effectiveness under clinical practice conditions, generation of drug resistance and the need to provide a second antileishmanial agent to protect against this disastrous event, and the ability to maintain reproductive contraceptive practices under routine clinical conditions.

A combined medical and surgical approach to hydatid disease: 12 years' experience at the Hospital for Tropical Diseases, London.

BACKGROUND: There is no consensus as to the most appropriate treatment for the varied and often complicated presentations of hydatid disease in Britain. We looked at our own results over a 12-year period to see if a consistent and logical plan had emerged. PATIENTS AND METHODS: 70 patients presenting between 1986 and 1998 were analysed retrospectively, with regard to their presentation, diagnosis, treatment and outcome, with particular reference to the use of chemotherapy, and to the difficulties of post-treatment assessment by serology and imaging. RESULTS: 37 patients had been treated previously. 35 had hepatic cysts and 26 multiple cysts. 4 patients were treated by surgery alone, 44 by chemotherapy and surgery, and 14 by chemotherapy alone. The combined use of albendazole and praziquantel pre-operatively reduced significantly the number of cysts that contained viable protoscolices: 1/25 versus 5/8 that received albendazole alone (P = 0.00013). During the 12-year period, it became our policy to aim for 3 months drug treatment (albendazole throughout with praziquantel for 2 weeks), re-assess and proceed either to surgery or to continue with chemotherapy. CONCLUSIONS: It is possible to construct an algorithm for the management of patients with hydatid disease by chemotherapy and surgery, but the assessment of results by indirect techniques remains difficult.

A policy for leishmaniasis with respect to the prevention and control of drug resistance.

At the moment no country has a policy designed to control or prevent drug resistance in leishmaniasis. The risk of resistance is high in areas of anthroponotic visceral leishmaniasis, for example North Bihar, India, where the rate in some areas is 60%. Post-epidemic Sudan is also at risk. Zoonotic areas in which HIV co-infection is common could also be at risk as sandflies can become infected from co-infected individuals. Many factors determine the choice of drug for the treatment of visceral leishmaniasis, and drug resistance may not be the over-riding priority. In anthroponotic areas reduction in transmission through public health measures will be important, but the use of two drugs in combination should be seriously considered. Pharmacokinetic and other features of the drugs available, relevant to their use in combination are discussed and tentative suggestions made concerning trials of possible combinations. These include miltefosine plus paromomycin and allopurinol plus an azole. Lessons may be learnt from the experiences of similar problems in malaria, leprosy and tuberculosis. Guidelines are offered for the introduction of policies to use drugs in combination, which differ between anthroponotic and zoonotic areas of transmission.

Subacute pulmonary granulomatous schistosomiasis: high resolution CT appearances--another cause of the halo sign.

A case of probable acute granulomatous pulmonary schistosomiasis is described with multiple focal opacities on chest radiography and widespread, but predominantly peribronchovascular, nodules with ground-glass halos on high resolution CT (HRCT). The HRCT appearances in early schistosomiasis have not been described previously. Although the features are not diagnostic and may be seen in other conditions, in the appropriate clinical context they may suggest pulmonary involvement in schistosomiasis. The features of pulmonary schistosomiasis in the different stages of infection are discussed. Pulmonary involvement should be suspected in patients with even minor respiratory symptoms when there is a history of exposure to fresh water in endemic areas.

Malaria at Christmas: risks of prophylaxis versus risks of malaria.

PIP: A large increase in the number of falciparum malaria cases imported into the UK was reported to the malaria reference laboratory in the first quarter of 1998. Contributory factors were unusually heavy rains in east Africa and a reduction in the use of the most effective antimalarial drug, mefloquine. There was also an increase in the number of cases of severe malaria in the UK. During December 1997 and January 1998, the Hospital for Tropical Diseases, London, treated 5 patients for severe malaria and gave advice on 20 more patients with malaria who had been admitted to intensive care units throughout England. 4 of the severe cases treated at the hospital are reported. In 3 of those 4 cases, incorrect, misleading, or inadequate advice was given by health care professionals. Media coverage of the adverse effects of antimalarial drugs has contributed to confusion about prophylactic regimens among both health care professionals and the public. The incidence of falciparum malaria among travellers who do not take prophylactic drugs is about 0.6% in east Africa and 3.5% in west Africa over a 2-week travel period. Travellers need to take measures to avoid being bitten by mosquitoes and should be taught to promptly seek medical help if they develop a fever while abroad or after they return. Moreover, using any one of the recommended prophylactic regimens is better than not using a potent regimen or no prophylaxis at all. Mefloquine is 90% protective against malaria in sub-Saharan Africa. While the efficacy of proguanil and chloroquine in 1987 was about 70% in west Africa and 50% in east Africa, those levels are now probably lower. The side effects of antimalarial drugs are discussed.^ieng

Efficacy and safety of liposomal amphotericin B (AmBisome) for visceral leishmaniasis in endemic developing countries.

Reported are the results of a study to determine the efficacy and safety of liposomal amphotericin B (AmBisome) for treating visceral leishmaniasis (kala-azar) in several developing countries where the disease is endemic (Brazil, India, and Kenya). At each study site, sequential cohorts of 10 patients each were treated with AmBisome at a dose of 2 mg.kg-1.day-1 (2 MKD). The first cohort received regimen 1:2 MKD on days 1-6 and day 10 (total dose: 14 mg/kg). If the efficacy with this regimen was satisfactory, a second cohort received regimen 2:2 MKD on days 1-4 and 10 (total dose: 10 mg/kg); and a third cohort received regimen 3:2 MKD on days 1, 5, and 10 (total dose: 6 mg/kg). In India, regimens 1, 2, and 3 (which were studied concurrently) each cured 100% of 10 patients. In Kenya, regimen 1 cured all 10 patients, regimen 2 cured 90% of 10 patients, but regimen 3 cured only 20% of 5 patients. In Brazil, regimen 1 was only partially curative: 5 of 13 patients (62%). Therefore, 15 patients were administered regimen 4 (2 MKD for 10 consecutive days; total dose, 20 mg/kg) and 13 patients were cured (83%). These results suggest that for the treatment of kala-azar the following doses of AmBisome should be administered: in India and Kenya, 2 mg/kg on days 1-4 and day 10; and in Brazil, 2 mg/kg on days 1-10.

PIP: The efficacy and safety of liposomal amphotericin B (AmBisome) for the treatment of visceral leishmaniasis (kala-azar) were evaluated in a phase II clinical trial conducted in Brazil, India, and Kenya--countries where kala-azar is endemic. At each study site, sequential cohorts of 10 patients each received three different dosage regimens of AmBisome. The first cohort received 2 mg/kg/day (MKD) on days 1-6 and day 10 (total dose, 14 mg/kg). If the efficacy of this regimen was satisfactory, the second cohort received 2 MKD on days 1-4 and day 10 (total dose, 10 mg/kg) and a third cohort was administered 2 MKD on days 1, 5, and 10 (total dose, 6 mg/kg). In India, all three regimens (studied concurrently) cured 100% of the total of 30 patients. In Kenya, the first regimen cured all 10 patients (100%), the second cured 9 of 10 patients (90%), and the third cured only 1 of 5 patients (20%). In Brazil, since the first regimen cured only 5 of 13 patients (62%), the next 15 patients were given 2 MKD for 10 consecutive days (total dose, 20 mg/kg); this intensified regimen cured 13 of the 15 patients (83%). Adverse effects were minor, primarily fever and chills associated with infusion and irregular pulse. These findings suggest that leishmaniasis patients in India and Kenya should receive 2 mg/kg of AmBisome on days 1-4 and day 10, while those in Brazil should be given 2 mg/kg on days 1-10. AmBisome treatment is especially recommended for those for whom standard agents are likely to be ineffective, toxic, or difficult to administer.

New World cutaneous leishmaniasis imported into Australia.

A case of cutaneous leishmaniasis in a traveller from Belize, Central America is reported. Leishmaniasis presents rarely in Australia and delays in diagnosis and treatment often occur. A high index of suspicion in a patient who has returned from an endemic region is required. Subsequent confirmation of a diagnosis of cutaneous leishmaniasis is best achieved by demonstration of the organism on skin biopsy, aspiration or smear. The histology is variable and depends on geographic, parasite species and host factors. Speciation of New World disease as either Leishmania braziliensis or Leishmania mexicana is important to determine the risk of later development of mucosal disease, which normally only occurs with L. braziliensis infection, and for optimal treatment. Several different modes of treatment have been suggested, but antimonials, such as sodium stibogluconate, remain the treatment of choice in New World cutaneous leishmaniasis.

Treatment of visceral leishmaniasis in children with liposomal amphotericin B.

We used liposomal amphotericin B as first-choice treatment of visceral leishmaniasis in 106 immunocompetent children who acquired the infection in a temperate region of southern Europe (Italy) where Leishmania infantum visceral leishmaniasis is endemic. The aim of the study was to identify the minimum total dose of liposomal amphotericin B needed to cure the infection in children and reduce the period of hospitalization. We conclude that the optimal regimen in immunocompetent children with L. infantum visceral leishmaniasis to be a total dose of 18 mg/kg of liposomal amphotericin B (3 mg/kg per day for 5 days, followed by 3 mg/kg administered as an outpatient regimen on day 10).

Disseminated infection due to Bipolaris australiensis in a young immunocompetent man: case report and review.

We report a case of disseminated infection due to Bipolaris australiensis in a 21-year-old immunocompetent Pakistani man. He presented with fever and jaundice. Examination revealed a mass in the right lung, mediastinal lymphadenopathy, a pericardial effusion, and abdominal masses obstructing and invading the common bile duct and right ureter. Histological examination and culture of a biopsy specimen of the hilar mass yielded the fungal pathogen B. australiensis. The patient was treated successfully with amphotericin B and itraconazole.

Imported mucocutaneous leishmaniasis.

We report a case of mucocutaneous leishmaniasis in a otherwise fit Caucasian man who had traveled in an endemic area. Initial tissue microscopy failed to identify the causative organism, which was only determined by subsequent culture as Leishmania braziliensis. This case illustrates the variability in the presence of Leishman-Donovan (LD) bodies in histopathological studies and emphasizes the need for culture in suspected cases of leishmaniasis, particularly given the ability of certain Leishmania species such as L. braziliensis to cause recalcitrant and destructive infections of the nose and mouth.